Local excesses of body fat are an important cause of aesthetic dissatisfaction, reduced self-esteem, and psychosocial distress. These excesses may involve, for example, prominent and undesired deposits of fat on the face, periorbital area, cheeks, chin, neck, chest, breast, abdomen, buttocks, hips, thighs, legs, and/or arms. One approach to reduce local excesses of body fat is to administer a fat-reducing drug. Some fat-reducing drugs are administered topically, i.e., to the skin surface.
Generally, the efficacy of a drug depends on the degree of drug exposure in the target tissue, e.g., the excess adipose tissue, e.g., subcutaneous fat. A standard measure of drug exposure is the area under the time-concentration curve (AUC) in the target tissue.
Many topical skin medications are used on a daily schedule, which is easy for users to remember. Furthermore, many daily skin medications, e.g., retinoids, acne medications, corticosteroids, antibiotics, antimycotics, and moisturizers, are left on the skin indefinitely and removed only incidentally, e.g., when the user next washes the skin.
Instructions that accompany many daily skin medications are silent as to whether and when the product should be removed. Thus, use of daily skin medications can routinely result in skin surface exposure for well over 12 hours, and in some cases 24 hours or more. These extended periods of skin surface exposure can be desirable when the therapeutic purpose is to treat the skin per se, because they maximize skin exposure over the dosage interval.
However, when the efficacy of a topical medication is determined by exposure in tissue other than the skin surface, an opportunity can exist to modify exposure beneficially in one tissue without compromise to the other. For example, exposure on the skin surface may merely be incidental to the route of delivery when exposure in subcutaneous fat (and the dermis adjacent to it) is more relevant to efficacy.
Therefore, there is a need for topical PFPRA dosage regimens to that improve patient comfort and convenience by reducing exposure on the skin surface without reducing exposure in subcutaneous fat and/or dermis.